Shopkeeper

Shopkeepers are present in every Shop and most Secret Rooms, and can also be found in Vaults, Arcades, Bedrooms, and I AM ERROR rooms. They cannot be hit by normal attacks, but explosions and certain items will damage them. Occasionally, destroying them will yield rewards.

Destroying a shopkeeper increases the chance for a Devil Room or Angel Room to appear by 10% for the current floor.

Normal Shopkeepers

Possible Rewards

Nothing (32.33% chance)
2 random Coins (32.33% chance)
2 Spiders (32.33% chance)
Steam Sale (1% chance)
Head of the Keeper (1% chance)
Coupon (1% chance once unlocked)

Special Shopkeeper

Special shopkeepers have a chance to replace regular shopkeepers. Special shopkeepers are unlocked by donating 234 coins to the Greed Donation Machine and special hanging shopkeepers are unlocked by donating 14 coins to the Greed Machine.

Possible Rewards

Nothing (~30.09% chance)
A Nickel / Sticky Nickel (66% chance)
Bloody Penny / Butt Penny / Counterfeit Penny / Flat Penny / Swallowed Penny / Burnt Penny (3.125% chance)
Greed (~0.78% chance)

Notes

Shopkeepers have 5 hit points, but most attacks capable of hitting them deal more damage than that.
Non-explosion attacks that can damage shopkeepers include The Boomerang, Red Candle, The Candle, Stitches, and Mars.
- The blast from Dark Arts will hit shopkeepers, but the slicing attack will not. This means an extra target is required to destroy a shopkeeper with Dark Arts.
- The blast from Camo Undies will hit shopkeepers.
- Collision damage from Mega Mush will hit shopkeepers.
- Shopkeepers can be grabbed with Suplex!. The shockwaves may also hit the Donation Machine.
With Infestation 2, destroying shopkeepers will spawn blue spiders.
Using the PAC1 F1SM Seed makes Shopkeepers invincible too.
If Greed appears after destroying a Special Shopkeeper, the doors will be locked.
Shopkeepers will be targeted by Mom's foot when using II - The High Priestess.
If Isaac already has Steam Sale, Head of the Keeper, and Coupon, Shopkeepers will not drop any further pedestal items.
If Isaac has Holy Light and hits an enemy near a Shopkeeper with a Holy Light tear, the Shopkeeper will be destroyed by the beam of light.
Special Shopkeepers can spawn in some specific room layouts even while not unlocked.

Unlockable Achievements

Lucky Toe - Blow up 20 Shopkeepers.

Trivia

The Shopkeeper's faces occasionally take on the appearance of certain popular Internet memes, such as "Forever Alone".
A Shopkeeper shares the appearance of a Dummy.
Edmund has confirmed that all Shopkeepers (and, by extension, Keeper) are mummified versions of Isaac from previous runs.^[1]